CORE D: SUMMARY Ikeno In order to determine the impact of an experimental intervention on aging, it is essential that investigators understand how an intervention alters pathological lesions that occur with age. Pathology increases exponentially with advancing age and is largely responsible for age-related morbidity and mortality. Pathological information also provides investigators with insight into the potential biological/molecular mechanism(s) of the intervention. Furthermore, pathological assessment of old animals is necessary to help investigators determine whether changes in the physiological and biochemical parameters measured are associated with or are independent of any underlying pathological conditions. In addition, pathological analysis of young animals provides investigators with information about genetic and pharmacological interventions that affect development. Thus, it is essential to obtain accurate and thorough pathological assessments of aging in both old and young animals. The Geroscience Pathology and Cellular Histology Core (GPCHC) will provide Project investigators with detailed pathological analyses of lesions that occur with age in the animals. The GPCHC will also provide investigators with cellular senescence characterization, histopathological, morphometric, and immunohistochemical analyses of specific lesions and tissues (e.g., neoplastic lesions, glomerulonephritis, gliosis in the brain, number and size of pancreatic islets, macrophage infiltration, and fat cell morphology in adipose tissue) obtained from the mice studied. In addition, the GPCHC will develop a comprehensive database of histopathological data and images of histopathology slides as a resource for: 1) trend analyses by the investigators; and 2) a tissue archive containing paraffin and frozen blocks for analysis of samples by request and for new morphological research. Furthermore, the GPCHC will provide investigators with histological support. We will prepare paraffin-embedded and frozen blocks, make unstained paraffin or frozen sections, and perform various histological staining techniques, including special staining. These data will allow investigators to evaluate the effects of genetic and pharmacological manipulations on the development of potentially fatal lesions and age-sensitive traits, and also provide information on whether the biochemical/molecular changes observed in the projects are correlated to the histopathological changes in specific tissues.